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Antibodies against ARHGDIB are associated with long‐term kidney graft loss
Author(s) -
Kamburova Elena G.,
Gruijters Maartje L.,
KardolHoefnagel Tineke,
Wisse Bram W.,
Joosten Irma,
Allebes Wil A.,
Meer Arnold,
Hilbrands Luuk B.,
Baas Marije C.,
Spierings Eric,
Hack Cornelis E.,
Reekum Franka E.,
Zuilen Arjan D.,
Verhaar Marianne C.,
Bots Michiel L.,
Drop Adriaan C. A. D.,
Plaisier Loes,
Melchers Rowena C. A.,
Seelen Marc A. J.,
Sanders Jan Stephan,
Hepkema Bouke G.,
Lambeck Annechien J. A.,
Bungener Laura B.,
Roozendaal Caroline,
Tilanus Marcel G. J.,
Voorter Christina E.,
Wieten Lotte,
Duijnhoven Elly M.,
Gelens Mariëlle A. C. J.,
Christiaans Maarten H. L.,
van Ittersum Frans J.,
Nurmohamed Shaikh A.,
Lardy Neubury M.,
Swelsen Wendy,
Pant Karlijn A. M. I.,
Weerd Neelke C.,
Berge Ineke J. M.,
Hoitsma Andries,
Boog Paul J. M.,
de Fijter Johan W.,
Betjes Michiel G. H.,
Heidt Sebastiaan,
Roelen Dave L.,
Claas Frans H.,
Bemelman Frederike J.,
Otten Henny G.
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15493
Subject(s) - medicine , hazard ratio , antibody , kidney transplantation , transplantation , autoantibody , kidney , gastroenterology , population , confidence interval , human leukocyte antigen , immunology , antigen , environmental health
The clinical significance of non‐ HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large‐scale studies incorporating analysis of multiple non‐ HLA antibodies simultaneously. We developed a multiplex non‐ HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non‐ HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP ‐dissociation inhibitor 2 ( ARHGDIB ) were significantly associated with graft loss in recipients transplanted with a deceased‐donor kidney (N = 3276) but not in recipients of a living‐donor kidney (N = 1496). At 10 years after deceased‐donor transplantation, recipients with anti‐ ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death‐censored covariate‐adjusted graft survival compared to the anti‐ ARHGDIB ‐negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32‐2.53; P = .0003). These antibodies occur independently from donor‐specific anti‐HLA antibodies (DSA) or other non‐ HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non‐ HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti‐ ARHGDIB antibodies in all patients awaiting deceased‐donor transplantation.